Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

Sampling for representative micropollutant loads in sewer systems.

Most commercially available auto-sampling devices do not support a continuous flow-proportional sampling mode, which would conceptually be the best for collecting representative composite samples. Instead different discrete sampling modes are available. Household chemicals can show considerable random short-term variations. With the anticorrosive benzotriazole, relating to a middle-frequent household activity, we show that, besides an accurate flow meter, mainly three factors are decisive for the representativeness of a substance's average load: the substance's load pattern, the sampling frequency and the length of the composite sample. When the sampling intervals are 10 minutes or longer, errors in the order of +/-40% (standard deviation) or more have to be accepted, if the substance of interest is contained in a low number of wastewater pulses (i.e., the level of household activity). This particularly holds true for specific pharmaceuticals e.g. carbamazepine. Ammonium would be less critical, because it relates to a larger number of sources in the same catchment.     

Antimutagenic activity of phenolic compounds, oligosaccharides and quinolizidinic alkaloids from Lupinus campestris seeds.

There are some foods that contain mutagenic or carcinogenic agents, some of which occur naturally and others that may be formed during preparation or cooking. Several foods such as legumes, also contain natural antimutagens and/or anticarcinogens. Lupine is one such legume that contains high amounts of protein (40%) and oils (14%). About 90 species of lupine have been reported throughout Mexico. However, the use of this crop as a source of food has been limited by the presence of antinutritional agents such as phenolic compounds (PC), carbohydrates (CH) and quinolizidinic alkaloids (Qas). It has also been suggested that consuming these compounds can affect human health and may even reduce the risk of disease. The objective of this work was to determine the effect of PC, CH and Qas, isolated and quantified from Lupinus campestris on the mutagenicity of 1-nitropyrene (1-NP) as a model mutagen and we used the Salmonella typhimurium tester strain YG1024 by the Kado microsuspension method. The results indicate that L. campestris seeds have 11 mg (+)catechin equivalent g(-1) seed coat; 120.3 mg g(-1) seeds and 2.13 mg g(-1) seeds of PC, CH and Qas, respectively. 1-NP mutagenicity was inhibited by 86% for PC, 76% for CH and 75% for Qas at concentrations of 200, 512 and 13.6 microg/tube, respectively.     

An alternating digital tree (ADT) algorithm for 3D geometric searching and intersection problems

A searching algorithm is presented for determining which members of a set of n points in an N dimensional space lie inside a prescribed space subregion. The algorithm is then extended to handle finite size objects as well as points. In this form it is capable of solving problems such as that of finding the objects from a given set which intersect with a prescribed object. The suitability of the algorithm is demonstrated for the problem of three dimensional unstructured mesh generation using the advancing front method.     

Optimal management of logistic activities in multi-site environments

The new emerging area of Enterprise Wide Optimization (EWO) has focused the attention in effectively solving the combined production/distribution scheduling problem. The importance of logistic activities performed in multi-site environments comes from the relative magnitude of the associated transportation costs and the good chance of getting large savings on such expenses. This paper first develops an exact MILP mathematical formulation for the multiple vehicle time-window-constrained pickup and delivery (MVPDPTW) problem. The approach is able to account for many-to-many transportation requests, pure pickup and delivery tasks, heterogeneous vehicles and multiple depots. Optimal solutions for a variety of benchmark problems with cluster/random distributions of pickup and delivery locations and limited sizes in terms of customer requests and vehicles have been discovered. However, the computational cost exponentially grows with the number of requests. For large-scale m-PDPTW problems, a local search improvement algorithm steadily providing a better solution through two evolutionary steps is also presented. A neighborhood structure around the starting solution is generated by first allowing multiple request exchanges among nearby trips and then permitting the reordering of nodes on every individual route. If a better set of routes is found, both steps are repeated until no improved solution is discovered. Compact MILP mathematical formulations for both sub-problems have been developed and solved through an efficient branch-and-bound algorithm. A significant number of large-scale m-PDPTW benchmark problems, some of them including up to 100 transportation requests, were successfully solved in reasonable CPU times.     

2,4,6‐Trichlorophenol and phenol removal in methanogenic and partially‐aerated methanogenic conditions in a fluidized bed bioreactor

A fluidized bed bioreactor (FBBR) was operated for more than 575 days to remove 2,4,6‐trichlorophenol (TCP) and phenol (Phe) from a synthetic toxic wastewater containing 80 mg L^?1 of TCP and 20 mg L^?1 of Phe under two regimes: Methanogenic (M) and Partially‐Aerated Methanogenic (PAM). The mesophilic, laboratory‐scale FBBR consisted of a glass column (3 L capacity) loaded with 1 L of 1 mm diameter granular activated carbon colonized by an anaerobic consortium. Sucrose (1 g COD L^?1) was used as co‐substrate in the two conditions. The hydraulic residence time was kept constant at 1 day. Both conditions showed similar TCP and Phe removal (99.9 + %); nevertheless, in the Methanogenic regime, the accumulation of 4‐chlorophenol (4CP) up to 16 mg L^?1 and phenol up to 4 mg L^?1 was observed, whereas in PAM conditions 4CP and other intermediates were not detected. The specific methanogenic activity of biomass decreased from 1.01 ± 0.14 in M conditions to 0.19 ± 0.06 mmolCH₄ h^?1 gTKN^?1 in PAM conditions whereas the specific oxygen uptake rate increased from 0.039 ± 0.008 in M conditions to 0.054 ± 0.012 mmolO₂ h^?1 gTKN^?1, which suggested the co‐existence of both methanogenic archaea and aerobic bacteria in the undefined consortium. The advantage of the PAM condition over the M regime is that it provides for the thorough removal of less‐substituted chlorophenols produced by the reductive dehalogenation of TCP rather than the removal of the parent compound itself. Copyright © 2005 Society of Chemical Industry     

Income, Time Effects and Direct Preferences in a Multimodal Choice Context: Application of Mixed RP/SP Models with Non-Linear Utilities

Transport problems typically involve at least two types of constraints, on income and on time. Therefore, the indirect utility function depends either on the income available after having subtracted the cost of the discrete alternative and on the free time left after having worked and travelled by each competing option. In the typical linear-in-the-attributes and in-the-parameters specification, that represents the first grade approximation of the indirect utility function, the effect of income and time constraints cancel out and only the cost and time of the alternatives matter in the comparison between them. From a microeconomic point of view this is equivalent to assume that income and time effects could be disregarded; which is not always the case. To account for these effects the utility function should include second order attributes; however, in non-linear utility functions it may not be easy to distinguish among several effects that could be relevant: direct preferences for good and leisure, and simple interactions between attributes other than income and time effects. This paper analyses these effects from a theoretical point of view focusing on the possible confounding problem in detecting income and time effects. We use a dataset collected for a modal choice context and containing both revealed and stated preference data, and estimate several NL models examining the effect of the different second-order terms on detecting income and time effects. We compared specifications including square cost and time attributes, interactions between time and cost, cost divided by the income available to be spent on free time, and time multiplied by free time. Our results confirm the strong effect of direct preferences for goods and leisure time on choice, and the potential confounding effect between quadratic attributes and other non-linear omitted terms. Finally, we also found that care should be taken in highlighting income and time effects using mixed data sources, since confounding effects can occur when non-linearities are accounted for in both data sets.     

A Web‐based and Group Learning Environment for Introductory Environmental Engineering

The use of computer‐based technology is becoming more prevalent in the classroom. As a part of an educational research project sponsored by the GE Foundation, strategies for augmenting a course, Introduction to Environmental Engineering (CE 280), were investigated including cross‐disciplinary experiences in teamwork, design, and the use of advanced teaching technologies such as the web. Interactive tools to assist student learning were developed and refined. Efforts have focused on developing an extensive website, web‐based quizzes and homework assignments, and tutorials. Base groups were used to provide both intellectual and emotional support to students. This paper summarizes the development of this course and the impact of rapid feedback on the progression of student understanding.     

Lipid damage in farmed rainbow trout (Oncorhynchus mykiss) after slaughtering and chilled storage

The flow ice system including ozone (OFI condition) was tested for slaughtering and storage (up to 16 days) of farmed rainbow trout (Oncorhynchus mykiss). Lipid damage analyses were carried out and compared to sensory acceptance and instrumental colour changes. Comparison to individuals processed with the flow ice system in the absence of ozone (FI condition) was undertaken. Rainbow trout slaughtered and chilled under FI and OFI conditions showed a low lipid damage development, according to lipid oxidation and hydrolysis events and lipid composition (polyunsaturated fatty acids, phospholipids and endogenous antioxidants) changes. Additionally, both icing conditions led to largely good quality and shelf life times and to the absence of changes in colour properties. It is concluded that flow ice as such, or including the presence of ozone, can be considered as ideal strategy to be employed as slaughtering and storage system during the commercialisation of the actual farmed species. The ozone presence has shown some profitable effects as leading to an extended shelf life time by quality retention of several sensory parameters; in contrast, some negligible negative effects could be observed on the secondary and tertiary lipid oxidation development. However, the oxidation values reached by individuals kept under OFI conditions cannot be considered as particularly high.